Phagocytic Dysfunction of Human Alveolar Macrophages and Severity of Chronic Obstructive Pulmonary Disease

Abstract

Alveolar macrophages in chronic obstructive pulmonary disease (COPD) have fundamental impairment of phagocytosis for nontypeable Haemophilus influenzae (NTHI). However, relative selectivity of dysfunctional phagocytosis among diverse respiratory pathogens: NTHI, Moraxella catarrhalis (MC), Streptococcus pneumoniae (SP), and nonbacterial particles, as well as the contribution of impaired phagocytosis to severity of COPD, has not been explored. Alveolar macrophages, obtained from nonsmokers (n = 20), COPD ex-smokers (n = 32), and COPD active smokers (n = 64), were incubated with labeled NTHI, MC, SP, and fluorescent microspheres. Phagocytosis was measured as intracellular percentages of each. Alveolar macrophages of COPD ex-smokers and active smokers had impaired complement-independent phagocytosis of NTHI (P = .003) and MC (P = .0007) but not SP or microspheres. Nonetheless, complement-mediated phagocytosis was enhanced within each group only for SP. Defective phagocytosis was significantly greater for NTHI than for MC among COPD active smokers (P < .0001) and ex-smokers (P = .028). Moreover, severity of COPD (FEV1%predicted) correlated with impaired AM phagocytosis for NTHI (P = .0016) and MC (P = .01). These studies delineate pathogen- and host-specific differences in defective alveolar macrophages phagocytosis of respiratory bacteria in COPD, further elucidating the immunologic basis for bacterial persistence in COPD and provide the first demonstration of association of impaired phagocytosis to severity of disease.